The farnesyl dibenzodiazepinone Compound 1 was isolated from Micromonospora sp. strains 046-ECO11and [S01]046, and was disclosed in U.S. Patent Application publication No. 2005/0043297, incorporated by reference in its entirety. Compound 1 was also disclosed in Charan et al. (2004), J. Nat. Prod., vol 67, 1431-1433, and Igarashi et al. (2005), J. Antibiot., vol 58, no 5, 350-352. Its use for the treatment of cancer is disclosed in US patent publication numbers 2005/0107363 and 2006/0079508, both incorporated herein by reference in their entirety.

Compound 1 was further shown to exhibit antibacterial activity, as well as binding or inhibitory activity against 5-lipoxygenase (5-LO), acyl CoA-cholesterol acyltransferase (ACAT), cyclooxygenase-2 (COX-2), the peripheral benzodiazepine receptor (PBR), and leukotriene cysteinyl (CysLT1) in US patent publication No. 2006/0079508, US Patent Application publication No. 2005/0043297 and in Canadian patent application 2,511,750, filed Jul. 21, 2005, all incorporated by reference in their entirety for all purposes. Most recently, Compound 1 was shown to be involved in the inhibition of the binding of ras-F to galectin (Gourdeau et al, Poster presented at 12th Meeting on Protein Phosphorylation and Cell Signaling, Salk Institute, La Jolla, Calif. Aug. 18-22, 2006).
Phosphate prodrugs have been produced for anticancer drugs, including ZD-6126 (N-acetylcolchinol-O-Phosphate, U.S. Pat. No. 6,423,753, issued to Dougherty) and Combretastatin A4 phosphate (U.S. Pat. No. 5,561,122, issued to Pettit) and A1 diphosphate (U.S. Pat. No. 7,078,552, issued to Pettit et al), all incorporated by reference in their entirety.
The farnesyl dibenzodiazepinone Compound 1 is highly lipophilic and is nearly insoluble in aqueous media. Formulation of Compound 1 thus often requires the use of solubilizers having some toxicity level, e.g. Cremophor EL™, poly(ethylene glycol)s or polysorbates. There is a need for a precursor of Compound 1 with improved chemical and biological properties, such as solubility and bioavailability. A highly desirable precursor would be a prodrug of Compound 1 stable enough to be formulated and administered, and which would release the active drug in vivo.